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Clinical Trial
. 2010 Feb;18(2):429-34.
doi: 10.1038/mt.2009.262. Epub 2009 Nov 24.

A phase I study of telomerase-specific replication competent oncolytic adenovirus (telomelysin) for various solid tumors

John Nemunaitis  1 , Alex W Tong, Michael Nemunaitis, Neil Senzer, Anagha P Phadke, Cynthia Bedell, Ned Adams, Yu-An Zhang, Phillip B Maples, Salina Chen, Beena Pappen, James Burke, Daiju Ichimaru, Yasuo Urata, Toshiyoshi Fujiwara
Affiliations
Clinical Trial

A phase I study of telomerase-specific replication competent oncolytic adenovirus (telomelysin) for various solid tumors

John Nemunaitis et al. Mol Ther. 2010 Feb.

Abstract

A phase I clinical trial was conducted to determine the clinical safety of Telomelysin, a human telomerase reverse transcriptase (hTERT) promoter driven modified oncolytic adenovirus, in patients with advanced solid tumors. A single intratumoral injection (IT) of Telomelysin was administered to three cohorts of patients (1 x 10(10), 1 x 10(11), 1 x 10(12) viral particles). Safety, response and pharmacodynamics were evaluated. Sixteen patients with a variety of solid tumors were enrolled. IT of Telomelysin was well tolerated at all dose levels. Common grade 1 and 2 toxicities included injection site reactions (pain, induration) and systemic reactions (fever, chills). hTERT expression was demonstrated at biopsy in 9 of 12 patients. Viral DNA was transiently detected in plasma in 13 of 16 patients. Viral DNA was detectable in four patients in plasma or sputum at day 7 and 14 post-treatment despite below detectable levels at 24 h, suggesting viral replication. One patient had a partial response of the injected malignant lesion. Seven patients fulfilled Response Evaluation Criteria in Solid Tumors (RECIST) definition for stable disease at day 56 after treatment. Telomelysin was well tolerated. Evidence of antitumor activity was suggested.

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Figures

<b>Figure 1</b>
Figure 1
Patient 308: Initial response of the largest of three metastatic melanoma lesions involving the right thigh.
<b>Figure 2</b>
Figure 2
Detection of Telomelysin viral DNA in patient plasma samples on various days post-treatment. Data represented at day 1 constituted peak values determined at up to 6 hours post-treatment. All patients exhibited below detection levels of plasma viral particles (≤400 vp/ml) at day 1 post-treatment.
<b>Figure 3</b>
Figure 3
Neutralizing antibody titer. Change in neutralizing antibody titer on day 28 after injection compared to baseline. *Patients 313 and 316 did not have day 28 plasma samples to determine post-treatment neutralizing antibody titer.
See this image and copyright information in PMC

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